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Safety and immunogenicity of DNA vaccines encoding Ebolavirus and Marburgvirus wild-type glycoproteins in a phase I clinical trial.

2015 Feb 15

Journal Article

Sarwar, U.N.; Costner, P.; Enama, M.E.; Berkowitz, N.; Hu, Z.; Hendel, C.S.; Sitar, S.; Plummer, S.; Mulangu, S.; Bailer, R.T.; Koup, R.A.; Mascola, J.R.; Nabel, G.J.; Sullivan, N.J.; Graham, B.S.; Ledgerwood, J.E.

J Infect Dis






Adult; Antibodies, Viral; Cytokines; Ebola Vaccines; Ebolavirus; Enzyme-Linked Immunospot Assay; Female; Humans; Male; Marburgvirus; Middle Aged; T-Lymphocytes; Vaccines, DNA; Viral Vaccines; Young Adult

BACKGROUND: Ebolavirus and Marburgvirus cause severe hemorrhagic fever with high mortality and are potential bioterrorism agents. There are no available vaccines or therapeutic agents. Previous clinical trials evaluated transmembrane-deleted and point-mutation Ebolavirus glycoproteins (GPs) in candidate vaccines. Constructs evaluated in this trial encode wild-type (WT) GP from Ebolavirus Zaire and Sudan species and the Marburgvirus Angola strain expressed in a DNA vaccine.METHODS: The VRC 206 study evaluated the safety and immunogenicity of these DNA vaccines (4 mg administered intramuscularly by Biojector) at weeks 0, 4, and 8, with a homologous boost at or after week 32. Safety evaluations included solicited reactogenicity and coagulation parameters. Primary immune assessment was done by means of GP-specific enzyme-linked immunosorbent assay.RESULTS: The vaccines were well tolerated, with no serious adverse events; 80% of subjects had positive enzyme-linked immunosorbent assay results (≥30) at week 12. The fourth DNA vaccination boosted the immune responses.CONCLUSIONS: The investigational Ebolavirus and Marburgvirus WT GP DNA vaccines were safe, well tolerated, and immunogenic in this phase I study. These results will further inform filovirus vaccine research toward a goal of inducing protective immunity by using WT GP antigens in candidate vaccine regimens.CLINICAL TRIALS REGISTRATION: NCT00605514.

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